This project is directed to the separation, characterization, definition of function of and mechanism of interactions among macrophages, thymus-derived cells and precursors of antibody-producing cells required for development and regulation of immune responses in tissue culture systems. The mechanism(s) of recognition of several different types of antigens by these cells will be thoroughly investigated. Special emphasis will be focused on the diverse regulatory mechanisms which enhance or suppress immunological reactivities of these cells. Combinations of in vivo and in vitro experimental systems will be used to provide the most direct approach to these critical problems. The mechanism of essential interactions of these cells with one another, including the role of physical contact and/or soluble products from stimulated cells which mediate these interactions will be analyzed. The mechanism(s) by which stimulated thymus-derived cells enhance or suppress induction of, or, already stimulated antibody responses in culture will be determined. Critical events in the development of immunoglobulin class-specific antibody responses will be investigated using suppressive effects of class-specific antibody to mouse immunoglobulin on the induction of antibody responses in vitro and on the development of precursors of antibody-producing cells in vivo. These studies will further the understanding of fundamental mechanisms involved in generation and regulation of expression of cellular and humoral immunity. This understanding should lead to a better understanding of mechanisms involved in development of pathologic conditions such as autoimmunity, allergic diseases, and immunodeficiency diseases, especially acquired forms. By understanding the mechanism by which cells specifically altered in their immune reactivity influence immune responses, better immunotherapy for treatment of these disease states should evolve.